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Controlled release of FGF‐2 using fragmin/protamine microparticles and effect on neovascularization
Author(s) -
Nakamura Shingo,
Kanatani Yasuhiro,
Kishimoto Satoko,
Nakamura Shinichiro,
Ohno Chizuko,
Horio Takuya,
Masanori Fujita,
Hattori Hidemi,
Tanaka Yoshihiro,
Kiyosawa Tomoharu,
Maehara Tadaaki,
Ishihara Masayuki
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32265
Subject(s) - protamine , fibroblast growth factor , materials science , neovascularization , proteolysis , heparin , pharmacology , biomedical engineering , chemistry , biochemistry , angiogenesis , medicine , cancer research , receptor , enzyme
Water‐insoluble fragmin/protamine microparticles of about 0.5–1 μm in diameter were prepared by simple mixing of low‐molecular‐weight heparin (fragmin) with protamine. We investigated the capability of these microparticles to immobilize fibroblast growth factor (FGF)‐2, to protect FGF‐2 against degradation, to enhance FGF‐2 activity, and to facilitate controlled release of FGF‐2. FGF‐2 bound to the fragmin/protamine microparticles with high affinity ( Kd = 2.08 × 10 −9 M ) and the half‐life of FGF‐2‐activity was prolonged substantially through binding of FGF‐2 to the microparticles, by protection of FGF‐2 from inactivation by heat and proteolysis. After subcutaneous injection into the back of mice, the fragmin/protamine microparticles underwent biodegradation and disappeared in about 2 weeks. A similar injection of FGF‐2‐containing microparticles resulted in significant neovascularization and fibrous tissue formation near the injection site after 1 week. These results indicate that controlled release of biologically active FGF‐2 occurs through both slow diffusion and biodegradation of the microparticles, with subsequent induction of neovascularization. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009